The objectives of this project are to study carbohydrate, amino acid, and ketone body metabolism in the ruminant with particular reference to gluconeogenesis, ketogenesis, and their metabolic control. Adult ruminants normally absorb little or no glucose since the rumen ferments the dietary carbohydrates to volatile fatty acids. Further, ketone bodies are produced by the rumen epithelium. A unique site of ketogenesis thus is present in ruminants and they must rely upon gluconeogenesis for nearly all of their metabolic glucose needs. Hypoglycemia and ketosis is a common problem during pregnancy and lactation. It thus is believed that the ruminant is an excellent animal model for a variety of metabolic studies. The present project may help elucidate the cause of the insufficient gluconeogenesis during ketosis as well as yield information on the mechanisms of ketogenesis. In addition, this study should aid in clarifying the basic metabolic adaptations the body undergoes in adapting to starvation, pregnancy, parturition, and lactation. In this project, the metabolism of amino acids is being stressed as well as the metabolism of other glucogenic and ketogenic substrates. A great deal of emphasis is being placed on measuring venoarterial concentration and 14 C differences and rates of blood flow across the liver, kidneys, gut and lower extremities (muscle). The simultaneous uptake and release of metabolites thus are measured and compared with the turnover in the whole body. The effects of acidosis, various hormonal perturbations, starvation, and pregnancy are being investigated.